Progress on each individual subproject is described in detail herein. Major areas of progress are summarized as follows: 1) 3-Methylfuran and carbon tetrachloride have been shown to be metabolized in vivo to highly reactive metabolites that cause necrosis of pulmonary Clara cells, emphasizing the importance of our earlier discovery that Clara cells are an important site of xenobiotic-metabolizing enzymes in lung. 2) The validity of a mechanism of acute renal tubular necrosis involving metabolic activation of a parent drug to an alkylating metabolite in situ by cytochrome P450-dependent enzymes has been demonstrated. 3) The importance of species and age differences in the specificity of target organ alkylation and toxicity by a metabolically activated alkylating agent has been demonstrated. 4) Immunochemical studies suggest that cytochrome b5 may play an important role in the metabolism of certain types of xenobiotics in the lung. 5) The glandular gastric mucosa of rats has been found to contain exceedingly high concentrations of reduced glutathione (GSH), raising the question of its potential physiologic significance as well as having important implications for gastric carcinogenesis. 6) A new clinical HPLC assay for 5-fluorouracil has been developed.